BMC Medicine最新文献

Background: Probiotics are widely used dietary supplements promoted to positively influence gut health and microbiota diversity, making them popular among healthy individuals. One of the purported benefits of probiotics is their ability to enhance gut microbiota diversity, a feature associated with improved resilience and overall health. However, evidence supporting this claim remains inconclusive. We aimed to investigate whether probiotics significantly modify gut microbiota diversity in healthy populations through a systematic review and meta-analysis.

Methods: A systematic search of MEDLINE, Embase, and Cochrane databases was conducted on 12/04/2024, following the search strategy registered in PROSPERO (CRD42022286137). Out of 9217 identified articles, 47 met the inclusion criteria of the current review, and 22 studies with data from 1068 individual subjects were eligible for meta-analysis of changes in gut microbiota diversity assessed by diversity indices. A random-effects model was employed to estimate the means of median differences (MedD) with 95% confidence intervals (CI) due to the expected heterogeneity.

Results: The quantitative synthesis revealed no statistically significant effects of probiotics on Shannon diversity (MedD = - 0.08, 95% CI [- 0.16 to 0.01]), observed operational taxonomic units (MedD = 2.19, 95% CI [- 2.20 to 6.57]), Chao1 (MedD = - 3.19, 95% CI [- 27.28 to 20.89]), or Simpson's index of diversity (MedD = - 0.01, 95% CI [- 0.02 to 0.00]) indices compared to unsupplemented controls. Subgroup and sensitivity analyses suggest that the probiotic taxonomic family, the risk of bias, or the duration of intervention did not change our findings. Insufficient data prevented us from meta-analysing other diversity indices; however, most of the included studies reported no difference in other reported α- and ß-diversity indices between the probiotic and control groups.

Conclusions: Our results indicate that probiotic supplementation does not produce statistically significant changes in gut microbiota diversity in healthy individuals. This study highlights the need for further research to determine whether specific probiotic strains or formulations may influence diversity in targeted subgroups or under specific conditions.

Background: Climate change has led to the increasing frequency of extreme high temperature events. However, few attentions have been paid to effective protective measures to mitigate the negative impacts of extreme high temperature. This study aimed to explore the relationship between long-term exposure to extreme high temperature and mortality, as well as effective protective measures.

Methods: We established a large cohort using medical and general health checks data from nearly 10 million people in Northwestern China between 2019 and 2023. We defined three distinct long-term extreme high temperature indicators based on the 99th percentile threshold of individual temperatures over the past 10 years: extreme high temperature durations (EHTD), extreme high temperature frequency (EHTF), and extreme high temperature severity (EHTS). A proportional hazards model was employed to explore the relationship between extreme high temperature and mortality, as well as to investigate the protective role of general health checks.

Results: For each unit increase in the EHTD, EHTF, and EHTS, the hazard ratio for mortality risk was 1.0022 (95% CI, 1.0020-1.0025), 1.0148 (95% CI, 1.0137-1.0159), and 1.0036 (95% CI, 1.0036, 1.0024-1.0048), respectively. However, when extreme high temperature was defined based on regional thresholds (county or city level) rather than individual thresholds (street level), there were no significant associations. Finally, we observed that general health checks' participants had a lower mortality risk from extreme high temperature exposure compared to non-participants.

Conclusions: Our study provided new evidence for assessing the adverse health effects of extreme high temperature. Moreover, this study highlighted that general health checks can effectively mitigate the negative health impacts of extreme high temperature.

Background: Existing evidence on the disease burden of smoking is often outdated and incomprehensive, particularly in Asia, which plays a pivotal role in the global tobacco control community. This study aimed to provide an updated and comprehensive estimate of the mortality and morbidity burden associated with smoking in Hong Kong.

Methods: This retrospective cohort study included adults with smoking status information recorded in the Hong Kong Hospital Authority database between 1 January 2008 and 31 December 2012. Subjects were classified into never-smokers, ex-smokers, and current smokers. The primary outcome was all-cause mortality. Cox proportional hazards regression, adjusted with fine stratification weighting and key baseline characteristics, yielded hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome.

Results: Of the 1,571,065 individuals analyzed, there were 14.3% current smokers, 11.9% ex-smokers, and 73.8% never-smokers. After a median follow-up of 11.7 years, 61,198 current smokers, 45,918 ex-smokers, and 220,947 never-smokers died. Significantly higher risks of all-cause mortality were observed among current smokers (HR [95% CI]: 1.53 [1.51-1.56]) and ex-smokers (1.33 [1.31-1.35]) than among never-smokers. Current and ex-smoking were positively associated with the incidences of 76 and 60 out of 115 morbidities, respectively. Strong associations were observed between smoking and increased risks of suicide (intentional self-harm), mental, and behavioral disorders due to psychoactive substance use and alcohol use, particularly among current smokers. Notably, these risks were higher in females than in males for all three outcomes. Additionally, females demonstrated higher risks of all-cause mortality, pneumonia, chronic obstructive pulmonary disease, and asthma compared to males.

Conclusions: Smoking remains a substantial burden on the healthcare system in Hong Kong, which may still be underestimated due to Hong Kong's relatively less advanced stage in the tobacco epidemic compared to some Western countries, where the full hazards of smoking have already manifested more prominently.

Background: Tranexamic acid, an antifibrinolytic drug, is effective for surgical hemostasis and bleeding-related disorders but may induce neurotoxicity, such as epilepsy. The mechanisms driving TXA-induced epilepsy remain poorly understood, as traditional toxicology approaches fall short in capturing its complex toxicity profile. This study employs network toxicology and molecular docking to elucidate the multi-target molecular mechanisms of TXA-induced epilepsy, aiming to enhance its safe clinical application.

Methods: TXA toxicity was predicted using ADMETlab2.0, PROTOX3.0, toxCSM, and ADMET-AI, with SMILES sequences obtained from PubChem, and a TXA target library was constructed using databases such as ChEMBL. EP-related targets were screened from databases such as GeneCards, and target intersections were analyzed using R software. Networks were constructed using Cytoscape and STRING, with GO and KEGG analyses performed to investigate molecular pathways. Molecular docking was conducted using the CB-Dock2 platform to analyze TXA binding to core targets.

Results: TXA poses a neurotoxicity risk, with 51 intersecting targets identified between TXA and EP, among which GABRA1, GABBR2, GABRA5, GABRA2, and GAD1 exhibited the greatest relevance. Analysis revealed that TXA induces EP by disrupting GABA signaling and synaptic function. The PPI network confirmed five core targets, and GO and KEGG analyses elucidated their roles in neural suppression. Molecular docking demonstrated stable binding of TXA to these targets, with Vina scores ranging from - 5.2 to - 6.9.

Conclusion: This study elucidates the mechanisms of TXA-induced EP through network toxicology and molecular docking, confirming its interference with GABA-related targets and neural suppression functions. The study overcomes the limitations of traditional toxicology, providing a scientific basis for the safe use of TXA and prevention of neurotoxicity.

Background: Postoperative delirium (POD) represents a significant challenge in perioperative care, particularly among older surgical patients. This acute neuropsychiatric syndrome is associated with prolonged hospitalization, increased mortality, and long-term cognitive decline. Sleep disturbance has emerged as a significant modifiable risk factor for POD. Sodium oxybate (SO), a gamma-aminobutyric acid B (GABA_B) receptor agonist with established sleep-enhancing properties, presents a promising therapeutic approach for POD prevention. The objective of this trial was to investigate whether prophylactic intraoperative sodium oxybate reduces POD incidence in older patients (≥ 65 years) undergoing major orthopedic surgery.

Methods: This randomized, double-blind, placebo-controlled trial enrolled 332 older patients undergoing elective spine and joint replacement surgery. Participants received either sodium oxybate (30 mg kg^-1) or saline after anesthetic induction. Stratified randomization allocated equal numbers to morning and afternoon surgery groups. The primary outcome was POD incidence within seven postoperative days, assessed using the Confusion Assessment Method (CAM).

Results: POD incidence showed no significant difference between groups in unstratified population (10.3% vs. 13.5%, P = 0.372). However, subgroup analysis revealed protective effects in morning surgery patients (7.3% vs. 18.5%, relative risk (RR) = 0.395, 95% confidence intervals (CI) = 0.161-0.968, P = 0.033), while no effect was observed in the afternoon surgery group (13.3% vs. 8.5%, P = 0.318). Among patients with delirium, no significant differences were observed in delirium severity, onset timing, delirium duration, or subtype distribution after false discovery rate (FDR) correction. No significant differences were found in sleep quality, maximal pain score, or safety parameters between groups after FDR correction.

Conclusions: Intraoperative sodium oxybate demonstrates possible time-specific efficacy, significantly reducing POD incidence exclusively in older patients undergoing morning orthopedic surgery, while demonstrating an acceptable safety profile with no significant adverse effects on anesthesia recovery or hemodynamic parameters, suggesting a potential chronotherapeutic approach to POD prevention.

Trial registration: Chinese Clinical Trial Registry, ChiCTR2300078594. Registered on 2023-12-13.

Background: Prostate cancer (PCa) is the second leading cause of death in men and is highly prone to metastasis. This study aims to develop the novel immuno-PET/CT tracer targeting trophoblast cell surface antigen 2 (Trop2), a transmembrane protein overexpressed in aggressive prostate malignancies, and to investigate its diagnostic value in preclinical studies as well as its potential utility in detecting metastases in PCa patients.

Methods: Integrated analysis of TCGA, GEO, and HPA datasets revealed Trop2 overexpression in prostate adenocarcinoma. By labeling two Trop2-targeted nanobodies (His-tagged T4 and His-tag-free RT4) with ⁶⁸Ga and ¹⁸F, we synthesized three radiotracers, [⁶⁸Ga]Ga-NOTA-T4, [¹⁸F]AlF-RESCA-T4, and [¹⁸F]AlF-RESCA-RT4. Preclinical validation included cellular assays and xenograft studies for ⁶⁸Ga/¹⁸F-T4 variants, followed by a first-in-human trial evaluating [¹⁸F]AlF-RESCA-RT4 in ten treatment-naïve PCa patients.

Results: Bioinformatics analysis demonstrated Trop2 as a promising target for PCa diagnosis and treatment. In preclinical studies, both [⁶⁸Ga]Ga-NOTA-T4 and [¹⁸F]AlF-RESCA-T4 illustrated high affinity to Trop2, specific tumor uptake (4.33 ± 0.38 %ID/g and 5.50 ± 0.69 %ID/g at 60 min, respectively) in Trop2-positive xenograft mouse models with minimal background distribution. In the translational study, [¹⁸F]AlF-RESCA-RT4 outperformed standard [¹⁸F]-FDG imaging in metastatic prostate cancer patients, detecting 62.4% more lymph node metastases (SUVmax 21.58 ± 13.12 vs. 4.80 ± 1.77) and 69.4% more bone lesions (SUVmax 7.83 ± 4.32 vs. 4.72 ± 1.22). No adverse events were observed.

Conclusions: This work successfully establishes that Trop2 is a new biomarker for PCa, and Trop2 immuno-PET/CT imaging can detect PCa lymph node and osseous metastases. The superior tumor-to-background contrast and clinical safety of [¹⁸F]AlF-RESCA-RT4 support its translational potential to guide Trop2-targeted therapies and enhance personalized treatment strategies.

Trial registration: NCT06851663. Retrospectively registered 02/24/2025.

Background: GLP-1 receptor agonists (GLP-1RA) are effective for glycemic control and cardiometabolic outcomes, but their infectious safety, particularly regarding herpes simplex virus (HSV) and herpes zoster (HZ), is underexplored. This study evaluated the association between GLP-1RA therapy and risks of HSV and HZ infections in patients with DM, compared to sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i).

Methods: We conducted a retrospective cohort analysis using target trial emulation principles on de-identified electronic health records from the TriNetX U.S. Network (2015-2022). Adults aged ≥ 18 years with diabetes prescribed biguanides were included. New users of GLP-1RA were compared to DPP-4i users in the first cohort and SGLT-2i users in the second cohort. Primary outcomes were HSV and HZ incidence, analyzed with Kaplan-Meier curves and Cox proportional hazards models.

Results: Among 95,190 GLP-1RA vs. DPP-4i pairs and 82,789 GLP-1RA vs. SGLT-2i pairs, GLP-1RA therapy was associated with higher risks of HSV (HR = 1.387, 95% CI = 1.249-1.539) and HZ (HR = 1.294, 95% CI = 1.203-1.392) compared to DPP-4i and HSV (HR = 1.277, 95% CI = 1.132-1.442) and HZ (HR = 1.18, 95% CI = 1.085-1.284) compared to SGLT-2i. Younger patients (18-50 years) on GLP-1RAs had elevated risks for HSV (HR = 1.632) and HZ (HR = 1.553). Female GLP-1RA users showed increased HSV risk (HR = 1.51), and poorly controlled patients (HbA1c ≥ 7%) had higher HSV risks (HR = 1.195). Herpes zoster vaccination mitigated these risks.

Conclusions: GLP-1RA use is associated with an increased risk of HSV and HZ infections compared with SGLT-2i or a DPP-4i use, especially in younger, female, and poorly controlled T2DM patients. Vaccination against herpes zoster is essential in mitigating these risks.

Background: Dysfunctional mitochondria are a prominent feature of myocardial ischemic-reperfusion (I/R) injury, but the clinical translation is scarce. Congenital dysbolism methylmalonic acidemia causes fatal mitochondrial lesions and premature death. However, the biological impact of mitochondrial metabolite methylmalonic acid (MMA) in the pathogenesis of I/R and its translational relevance were unknown.

Methods: MMA and relevant metabolites were measured in 3 independent human cohorts and animals. Cardiac Mmut-conditional knockout (endogenous MMA elevation) and exogenous MMA administration were conducted in mouse I/R model. The potential mechanism was explored through multiomics, chromatin immunoprecipitation, and site-directed mutagenesis assays. The translational value of targeting MMA metabolism was assessed in a porcine I/R model.

Results: Circulating MMA predicts myocardial injury or heart failure risk post-reperfusion, which outmatches its isomer succinate in humans. Both MMA and succinate were elevated in heart tissues of mice at the initial period post-I/R, while later, MMA maintained higher levels, but succinate rapidly decreased to baseline levels. Endogenous and exogenous MMA, not succinate, increased susceptibility to myocardial I/R injury and mitochondrial dyshomeostasis, including impaired mitochondrial bioenergetics, biogenesis, and renovation. Mechanistically, MMA elevation inhibited the deacetylase activity of SIRT1; thus, hyperacetylation of transcription factor CREB^K309 blunted its binding to the BNIP3 promoter and inhibited BNIP3-mediated mitochondrial quality control. Adeno-associated virus 9-containing MMUT gene delivery ameliorated impaired MMA metabolism to improve mitochondrial quality and cardiac phenotypes in I/R pigs.

Conclusions: This study revealed an unrecognized harmful effect of MMA on myocardial vulnerability distinct from its isomer succinate. Targeting MMA metabolism represents a promising strategy to optimize risk stratification and mitigate myocardial injury in patients with AMI.

Background: Hysterectomy prevalence varies from 4 to 41% across populations, but the rates in China and the risk factors remain unclear. The study aimed to estimate the prevalence of hysterectomy in Chinese and explore the potential risk factors.

Methods: A multicenter cross-sectional study was conducted with Meinian health screening center chain across 31 provinces of China between January 2017 and December 2018. Data from 9,013,462 participants aged ≥ 18 years were extracted for the current study. The geographic variation of hysterectomy prevalence was illustrated with different colors on the national map of China. Relative risk (RR) and 95% confidence intervals (CIs) from log-binomial regression were used to estimate the associations between hysterectomy and metabolic disorders.

Results: The age-standardized prevalence of hysterectomy in China was 2.36% (95% CIs, 2.35-2.37), with the highest in the Jiangsu Province (3.26%) and Northeast region (2.67%). Women aged 55-59 years had the highest prevalence of hysterectomy (7.61%). Hysterectomy was positively associated with obesity [RR, 1.31 (95% CIs, 1.29-1.32)]; hypertension [1.22 (1.21-1.23)]; diabetes [1.26 (1.24-1.28)]; hyperglycemia [1.22 (1.20-1.23)]; dyslipidemia [1.18 (1.16-1.19)]; metabolic associated fatty liver disease [1.25 (1.24-1.26)]; and metabolic syndrome [1.18 (1.16-1.21)]. In the 18-34 years age group, the positive associations of hysterectomy with diabetes and hypertension were 6.09 (4.48-8.26) and 6.08 (5.18-7.14).

Conclusions: In this large-scale study, the prevalence of hysterectomy was higher among menopausal women or those living in the East and Northeast regions. Hysterectomy was strongly associated with metabolic disorders, especially in women of childbearing age. Further studies were warranted to elucidate the underlying mechanisms and develop public health policies.

Background: Cystatin C may better assess cardiovascular risk than serum creatinine for kidney function, but its accuracy may vary by sex. We evaluated sex differences in cardiac risk using estimated kidney function from either biomarker.

Methods: We included all adults from the UK Biobank without prior cardiac event who had kidney function and baseline data. We defined cardiac events and deaths using ICD-10 codes in hospital or death records. We fitted cause-specific Cox models to evaluate sex differences in cardiac outcomes using estimated glomerular filtration (mL/min/1.73m²) from serum creatinine (eGFRCr), cystatin C (eGFRCys) and both (eGFRCr-Cys).

Results: Among 394,920 adults (55% female), 19,689 (9%) females and 28,540 (16%) males had cardiac events. In adjusted models, eGFRCys and eGFRCr-Cys showed stronger associations with increased cardiovascular risk in females than when using eGFRCr (p < 0.001). Females with eGFRCys 45-59 had elevated cardiac risk (HR 1.08, 95% CI 1.03-1.14) compared to males with eGFRCys 90-104-an effect not seen with eGFRCr or eGFRCr-Cys. eGFRCr showed a J-shaped association with cardiac risk, being increased in males but reduced in females when eGFRCr ≥ 105 (females: HR 0.65, 95% CI 0.61-0.69; males: HR 1.18, 95% CI 1.12-1.24 versus males with eGFRCr 90-104). The risk of cardiac events was more linear in adjusted models with eGFRCys.

Conclusions: Measurement of cystatin C improves estimation of cardiac risk associated with kidney function, particularly for females. Incorporating eGFRCys, rather than eGFRCr, into cardiovascular risk assessment may be more important for early detection and management of high-risk females with CKD.